Vesa P Hytonen and Armando Del Rio Hernandez
University of Tampere, Finland
Fimlab Laboratories, Tampere, Finland
Imperial College London, UK
Scientific Tracks Abstracts: J Proteomics Bioinform
Talin is cytoplasmic protein connecting integrin receptors to actomyosin network. This linkage is essential for cell anchoring and spreading and naturally also for development. Talin acts as a hub for molecular interactions in focal adhesions and the interactions between talin and binding partners are regulated by mechanical signals. We study the mechanical response of talin by steered molecular dynamics. Both constant force and constant velocity simulations in explicit water have been found useful to explore the molecular features of talin. We have found talin rod subdomains to differ from each other in terms of their mechanical stability. Importantly, we have been able to compare and validate the results by using experimental data obtained with single-molecule atomic force microscopy. Destabilizing point mutations applied on talin rod have been found to cause significant changes in cell spreading, migration and cellular traction force. Our recent studies focus on mechanically weakened talin forms, intermediates of protein unfolding and engineering of unfolding-resistant talin forms. Recent Publications 1. Haining A W, von Essen M, Attwood S J, Hytönen V P and Del Río Hernández A (2016) All subdomains of the talin rod are mechanically vulnerable and may contribute to cellular mechanosensing. ACS Nano 10:6648-58. 2. Hytönen V P and Wehrle-Haller B (2016) Mechanosensing in cell-matrix adhesions - Converting tension into chemical signals. Experimental Cell Research 343:35-41. 3. Haining A W M, Rahikainen R, Cortes E, Lachowski D, Rice A, von Essen M, Hytönen V P and Del Río Hernández A (2018) Mechanotransduction in talin through the interaction of the R8 domain with DLC1. PLoS Biology 16:e2005599. 4. Mykuliak V V, Haining A W M, von Essen M, Del Río Hernández A and Hytönen V P (2018) Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin. PLoS Computational Biology 14:e1006126.